Citations

There is a growing body of evidence that suggests a connection between traumatic brain injury (TBI) and subsequent post-traumatic stress disorder (PTSD). While the exact mechanism is unknown, we hypothesize that chronic glutamate neurotoxicity may play a role. The consumption of dietary glutamate is a modifiable factor influencing glutamate levels in the blood and, therefore, in the brain. In this systematic review, we explored the relationship between dietary glutamate and the development of post-TBI PTSD. Of the 1748 articles identified, 44 met the inclusion criteria for analysis in this review. We observed that individuals from countries with diets traditionally high in glutamate had greater odds of developing PTSD after TBI (odds ratio = 15.2, 95% confidence interval 11.69 to 19.76, p < 0.01). These findings may support the hypothesis that chronically elevated blood glutamate concentrations caused by high dietary intake invoke neurodegeneration processes that could ultimately result in PTSD. Further studies will clarify whether lowering glutamate via diet would be an effective strategy in preventing or treating post-TBI PTSD.

Background: Peripheral nerve injury (PNI) following revision total hip arthroplasty (rTHA) can be a devastating complication. This study assessed the frequency of and risk factors for postoperative PNI following rTHA. Methods: Patients who underwent rTHA from 2003 to 2015 were identified using the National Inpatient Sample (NIS). Demographics, medical history, surgical details, and complications were compared between patients who sustained a PNI and those who did not, to identify risk factors for the development of PNI after rTHA. Results: Overall, 112,310 patients who underwent rTHA were identified, 929 (0.83%) of whom sustained a PNI. Univariate analysis found that younger patients (p < 0.0001), females (p = 0.025), and those with a history of flexion contracture (0.65% vs. 0.22%, p = 0.005), hip dislocation (24.0% vs. 18.0%, p < 0.001), and spine conditions (4.8% vs. 2.7%, p < 0.001) had significantly higher rates of PNI. In-hospital complications associated with PNI included postoperative hematoma (2.6% vs. 1.2%, p < 0.0001), postoperative seroma (0.75% vs. 0.30%, p = 0.011), superficial wound dehiscence (0.65% vs. 0.23%, p = 0.008), and postoperative anemia (36.1% vs. 32.0%, p = 0.007). Multivariate analysis demonstrated that a history of pre-existing spine conditions (aOR: 1.7; 95%-CI: 1.3–2.4, p < 0.001), prior dislocation (aOR 1.5; 95%-CI: 1.3–1.7, p < 0.001), postoperative anemia (aOR 1.2; 95%-CI: 1.0–1.4, p = 0.01), and hematoma (aOR 2.1; 95%-CI: 1.4–3.2, p < 0.001) were associated with increased risk for PNI. Conclusions: Our findings align with the existing literature, affirming that sciatic nerve injury is the prevailing neuropathic complication after total hip arthroplasty (THA). Furthermore, we observed a 0.83% incidence of PNI following rTHA and identified pre-existing spine conditions, prior hip dislocation, postoperative anemia, or hematoma as risk factors. Orthopedic surgeons may use this information to guide their discussion of PNI following rTHA, especially in high-risk patients.

Abstract Background: The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine. Methods: Patients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis. Results: Sixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0%, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7%, p = 0.714) and OS (94.6% vs. 93.8%, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw. Conclusions: In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial. Trial Registration This is a clinical trial registered under NCT02301611.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Abstract Rationale Endotracheal intubation is the third most common bedside procedure in U.S. hospitals. In over 40% of intubations, preventable complications attributable to human factors occur. A better understanding of team dynamics during intubation may improve patient safety. Objectives To explore team dynamics and safety-related actions during emergent endotracheal intubations in the emergency department and intensive care unit and to engage members of the care team in reflection for process improvement through a novel video-based team debriefing technique. Methods Video-reflexive ethnography involves in situ video recording and reflexive discussions with practitioners to scrutinize behaviors and to identify opportunities for improvement. In this study, real-time intubations were recorded in the emergency department and intensive care unit at Mayo Clinic Rochester, and facilitated video-reflexive sessions were conducted with the multidisciplinary procedural teams. Themes about team dynamics and safety-related action were identified inductively from transcriptions of recorded sessions. Results Between December 2022 and January 2023, eight video-reflexive sessions were conducted with a total of 78 participants. Multidisciplinary members included nurses (n = 23), respiratory therapists (n = 16), pharmacists (n = 7), advanced practitioners (n = 5), and physicians (n = 26). In video-reflexive discussions, major safety gaps were identified and several solutions were proposed related to the use of a multidisciplinary intubation checklist, standardized communication and team positioning, developing a culture of safety, and routinely debriefing after the procedure. Conclusions The findings of this study may inform the development of a team supervision model for emergent endotracheal intubations. This approach could integrate key components such as a multidisciplinary intubation checklist, standardized communication and team positioning, a culture of safety, and debriefing as part of the procedure itself.